[unreadable] Chemical synthesis provides the capacity to produce chemotherapeutic agents, and chemical reactions are the irreplaceable tools of the medicinal chemist engaged in the drug discovery process. Advances in chemical reaction technology reduce the interval between the conception of the chemical entity as a potential drug candidate and its synthesis for subsequent biological evaluation. As a consequence, the synthesis activity is a critical discipline that continues to have an important impact upon the fields of both medicine and biology. The present grant will continue to address the development of new stereoselective reactions which are relevant to the synthesis of antibiotic and antinepolastic agents derived from amino acid constituents. The methodological studies dealing with new reaction discovery will emphasize the development of chiral metal catalysts for the synthesis of complex amino acids. These advances should culminate in practical routes to the asymmetric synthesis of beta-hydroxy-alpha-amino acids and alpha, beta-diamino acids. Synthesis targets associated with this project will include the antiviral cyclic heptapeptide cyclomarin A, the marine toxin, azaspiracid 1, and the cytotoxic hexacyclic alkaloid daphnicyclidin A. [unreadable] [unreadable]